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Year : 2020  |  Volume : 63  |  Issue : 4  |  Page : 661-662
Inverted condyloma of the cervix: A rare mimicker of a high-grade cervical lesion

1 Division of Cytopathology, ICMR-National Institute of Cancer Prevention and Research, Noida, Uttar Pradesh, India
2 Division of Clinical Oncology, ICMR-National Institute of Cancer Prevention and Research, Noida, Uttar Pradesh, India

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Date of Submission25-Oct-2019
Date of Decision31-Dec-2019
Date of Acceptance03-Jan-2020
Date of Web Publication28-Oct-2020

How to cite this article:
Gupta R, Dhanasekaran K, Hariprasad R, Gupta S. Inverted condyloma of the cervix: A rare mimicker of a high-grade cervical lesion. Indian J Pathol Microbiol 2020;63:661-2

How to cite this URL:
Gupta R, Dhanasekaran K, Hariprasad R, Gupta S. Inverted condyloma of the cervix: A rare mimicker of a high-grade cervical lesion. Indian J Pathol Microbiol [serial online] 2020 [cited 2022 Jun 30];63:661-2. Available from: https://www.ijpmonline.org/text.asp?2020/63/4/661/299329

Genital warts, which are caused by low-risk types of human papilloma virus (HPV), display three histologic patterns: flat, papillomatous, and inverted.[1] Inverted condyloma poses a diagnostic challenge for the gynaecologists as well as histopathologists due to the possibility of overdiagnosis as invasive carcinoma.[2]

A 27-year-old married nulliparous female presented to the health promotion clinic at our Institute for evaluation of leucorrhea of 6-month duration. Per speculum examination showed a hypertrophied cervix. Cervical smear was reported as negative for intraepithelial lesion or malignancy [Figure 1]a. Visual examination with acetic acid as well as Lugol's iodine (VIA/VILI) were positive at 6 o'clock and 12 o'clock positions. Colposcopic findings suggested a low-grade lesion at 12 o'clock and high-grade lesion at 5–7 o' clock [Figure 1]b. Hence, directed biopsies were taken from both these lesions for histopathological examination.
Figure 1: Cervical smear (a, Papanicolaou stain, 10×) showing cytologically unremarkable superficial and intermediate squamous cells. Colposcopic image (b) showing low-grade lesion at 12 o' clock (arrowhead) and high-grade lesion from 5 to 7 o' clock (arrows)

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Biopsy from low-grade lesion showed features of CIN 1 encompassing focal HPV-associated changes [Figure 2]a. On the other hand, biopsy from the high-grade lesion revealed an endophytic lesion composed of lobules and nests of squamoid cells [Figure 2]b and c] with focal koilocytotic change [Figure 2]d. There was no evidence of dysplasia in the endophytic epithelial nests or the overlying epithelium. Surrounding stroma showed mild chronic inflammation. Based on the histopathological features, a final diagnosis of inverted condyloma, posterior lip of uterine cervix, was rendered. In view of high-grade lesion involving more than 2 quadrants of the cervix, loop electrosurgical excision procedure (LEEP) was planned. However, the patient requested for time to discuss with her family. She returned to the clinic 8 weeks after the initial visit and at this visit, she was found to be 5 weeks pregnant. Hence, the procedure was deferred and she was advised for repeat colposcopy after 3 months of her delivery for re-evaluation and further management.
Figure 2: Photomicrograph of biopsy from the low-grade lesion showing CIN 1 changes (a, H and E 40×). Biopsy from the colposcopic high-grade lesion demonstrates inward proliferation of squamoid cell nests (b, H and E, 10×). Higher magnification (c, H and E, 40×) shows the absence of dysplastic features in the squamous nests. Focal HPV-induced change is noted (arrow, d, H and E, 40×)

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Human papilloma virus (HPV), especially the high-risk oncogenic types, has been established to play a central role in cervical carcinogenesis. On the other hand, low-risk or non-oncogenic types of HPV are associated with occurrence of genital warts, both in females and males.[3] The landmark papers by Meisels et al. provided important information on cervical condylomata.[3],[4]

Histologically, cervical condylomatous lesions have one of the three patterns: (a) flat condyloma; (b) papillomatous condyloma; and (c) endophytic or inverted condyloma. A study of 289 cervical condylomatous lesions reported flat type as the most frequent (78.9%) followed by inverted (14.5%) and papillomatous variety (6.6%).[1] However, colposcopic patterns of condylomatous lesions have been described as: (1) condyloma planum or flat condyloma—most common; (2) slightly raised condyloma with tiny projections (asperities); (3) papillomatous condyloma; and (4) condylomatous cervico-vaginitis.[2] The inverted pattern of condyloma cannot be accurately identified on colposcopy due to the inward nature of the lesion. The same was true in our case. In view of the VIA/VILI-positive lesion on the posterior lip of the cervix along with the atypical vascular pattern of the lesion, a colposcopic impression of high-grade lesion was made. The rarity of this lesion is evident from the paucity of cases describing the colposcopic features of inverted condyloma.

An extensive review of the literature revealed only an occasional report of inverted condyloma[5] and that too, with histopathology findings only. Cytological features of an inverted condyloma have not been described adequately in the available literature, again attesting to the paucity of literature on this lesion. Cervical smear in cases of inverted condyloma may demonstrate koilocytes intermixed with dyskeratotic cells, as a marker of HPV infection.[2] In the present case, koilocytes were not observed on the cervical smear, even on review. This could be explained by the focal nature of HPV-associated changes seen in the biopsy sections with these cells concentrated mainly in the endophytic epithelial nests, making it difficult for these koilocytes to be scraped into the smear.

The most important histopathologic differential diagnosis is an invasive carcinoma, in view of the predominant endophytic nature of the epithelial proliferation.[2] The clues to a precise diagnosis in such cases are the regular contour of the endophytic epithelial nests, representing the replacement of endocervical glands by condylomatous epithelium, presence of koilocytes and absence of the characteristic nuclear features of dysplasia. In the present case, a precise histological diagnosis of inverted condyloma could be made by recognition of the characteristic morphologic features. Immunohistochemical expression of Ki-67 and p16 may also assist in the differentiation of inverted condyloma from high-grade lesions.[6] The other entities demonstrating an inverted growth pattern include inverted immature metaplasia and inverted transitional cell papilloma. The former is composed of intermediate-sized squamous cells with semblance to immature metaplastic cells having mild nuclear atypia, small nucleoli, and pale cytoplasm. The latter, on the other hand, shows complex inverted growth of cells with transitional features like peripheral palisading, regimented nuclei, nuclear grooves, and focal microcysts.[6]

In view of the rarity of inverted condyloma of cervix, the potential of malignant transformation is not clearly known. Nevertheless, the association of HPV with pathogenesis of this lesion does lend a possibility of it turning malignant at some point of time, especially if accompanied by high-risk types of HPV.[5]

In conclusion, this case is being reported to highlight the rarity of inverted condyloma of the uterine cervix and the possibility of this lesion mimicking a high-grade lesion on colposcopy. In view of the endophytic nature of the lesion, there is a likelihood of it being missed on cervical cytology as well. Histopathology is mandatory to arrive at a precise diagnosis of this rare entity and facilitate appropriate management.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Syrjänen K. Condylomatous lesions of the uterine cervix with special reference to squamous cell carcinogenesis. Gynecol Obstet Invest 1980;11:350-64.  Back to cited text no. 1
Ferenczy A. Benign lesions of the cervix. In: Blaustein A, editor. Pathology of the Female Genital Tract. 2nd ed. New York, Springer-Verlag; 1982. p. 147-9.  Back to cited text no. 2
Meisels A, Fortin R. Condylomatous lesions of the cervix and vagina: Cytological patterns. Acta Cytol 1976;20:505-9.  Back to cited text no. 3
Meisels A, Fortin R, Roy M. Condylomatous lesions of the cervix. II. Cytologic, colposcopic and histopathologic study. Acta Cytol 1977;21:379-90.  Back to cited text no. 4
Charles DP, Narmadha P, Viswanathan P, Manohar U. Inverted condyloma of uterine cervix: A rare condylomatous lesion. J Evol Med Dent Sci 2014;3:12526-30.  Back to cited text no. 5
Stewart CJ, Frost F, Ruba S. Inverted immature metaplasia of the uterine cervix. Pathology 2010;42:174-7.  Back to cited text no. 6

Correspondence Address:
Sanjay Gupta
Division of Cytopathology, ICMR.National Institute of Cancer Prevention and Research, I-7, Sector-39, Noida - 201 301, Utter Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_838_19

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